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Physiology > Endocrine 5 > Flashcards

Endocrine 5 Flashcards

1
Q

How much calcium in adult human?

A

approx 1 kg

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2
Q

Form of Ca2+ in body

A

99% in crystalline form within the skeleton and teeth.
0.9% intracellularly within the soft tissues.
<0.1% present in the extracellular fluid (ECF)

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3
Q

Where is ECF Ca2+ present (bound? etc)?

A
  • 1 half - either bound to plasma proteins or complexed with PO43-, not available for cellular reactions
  • Other half can readily pass to from plasma into ICF and interact with the cells.
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4
Q

What of ECF Ca2+ is biologically active and subject to regulation?

A

Only free ECF Ca2+

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5
Q

How much does free ECF Ca2+ constitutes in the body.

A

Less than one thousandth of the total calcium

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6
Q

Physiological role of Calcium x 13

A
  • Muscle contraction
  • Structural integrity of bones and teeth
  • Blood clotting
  • Enzyme regulation
  • Membrane stability
  • DNA/RNA synthesis
  • Neurotransmitter release
  • Secretion
  • Intracellular signaling
  • Proliferation
  • Fertilization
  • Cell motility
  • Maintenance of tight junctions
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7
Q

Roles of Free ECF Ca2+

A
  1. To prevent aberrant neuromuscular excitability
  2. Excitation-contraction coupling
  3. Stimulus – secretion coupling
  4. Excitation – secretion coupling
  5. Maintenance of tight junctions
  6. Clotting of Blood
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8
Q

Role of Free ECF Ca2+ in preventing aberrant neuromuscular excitability

A

A fall in free Ca2+ causes overexcitability of nerves and muscles; A rise in free Ca2+ depresses neuromuscular excitability.

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9
Q

Role of Free ECF Ca2+ in excitation-contraction coupling

A

Excitation-contraction coupling in cardiac and smooth muscle – resulting from increased Ca2+ permeability in response to an action potential.

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10
Q

Role of Free ECF Ca2+ in stimulus – secretion coupling

A

Entry of Ca2+ into secretory cells, triggers the release of secretory products by exocytosis
- Important for release of Neurotransmitters by nerve cells and for peptide and catecholamine hormone secretion by endocrine cells.

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11
Q

Entry of Ca2+ into secretory cells is caused by…..

A

Increased permeabilty to Ca2+ in response to appropriate stimulation

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12
Q

Role of free ECF Ca2+ in excitation – secretion coupling

A

In Pancreatic b cells, Ca2+ entry leads to insulin secretion.

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13
Q

Role of free ECF Ca2+ in maintenance of tight junctions between cells

A

Ca2+ forms some of the intracellular cement that holds particular tight junctions together.

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14
Q

Role of free ECF Ca2+ in clotting of blood

A

Ca2+ acts as a co-factor in several steps of the cascade that lead to clot formation.

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15
Q

Function of skeleton (involving calcium)

A

Storage depot for Ca2+ and PO43-, which can be exchanged with the plasma to maintain plasma concentrations of these electrolytes.

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16
Q

3 types of bone cell

A
  • Osteoblasts
  • Osteocytes
  • Osteoclasts
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17
Q

Function of osteoblasts

A

Secrete extracellular organic matrix within which the Ca3(PO4)2 crystals precipitate.

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18
Q

Function of osteocytes

A

Retired osteoblasts imprisoned within the bony wall they have deposited around them.

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19
Q

Function of osteoclasts

A

Reabsorb bone in their vicinity; break down the organic matrix.

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20
Q

Where do osteoblasts and osteoclasts trace their origins to?

A

Bone marrow

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21
Q

What are osteoblasts derived from?

A

Stromal cells

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22
Q

What are stromal cells?

A

Type of connective tissue in the bone marrow.

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23
Q

Where are osteoclasts derived from?

A

Differentiate from macrophages, tissue bound derivatives of monocytes

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24
Q

What do osteoblasts and their immediate

precursors produce in unique communication system?

A

2 chemical signals that govern osteoclast development and activity in opposite ways – they are RANK ligand and Osteoprotegerin.

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25
Q

Role of osteoblasts in governing osteoclast development and activity diagram

A
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26
Q

What does mechanical stress favour?

A

Bone deposition

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27
Q

Child – bone builders keep ahead of the bone destroyers - what is this influenced by?

A

IGF1 and GH

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28
Q

IGF1

A

Insulin-like growth factor 1

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29
Q

What do mechanical factors do?

A

Adjust the strength of bone in response to demands placed on it.

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30
Q

Bone mass with age

A
  • Decreases

- Peaks at 30, then declines after age 40. By 50-60 years bone resorption often exceeds bone formation.

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31
Q

The greater the physical stress….

A

the greater the rate of bone deposition.

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32
Q

Osteopososis bone changes

A

Reduced deposition of the bones organic matrix – reduced osteoblast activity and/or increased osteoclast activity.

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33
Q

Osteoporosis risk age

A

Occurs in greatest frequency in perimenopausal and postmenopausal women.

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34
Q

Skeleton of elderly vs peak women

A

Skeletons of elderly women are only about 50-80% as their peak at age 35.

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35
Q

Skeleton of elderly vs peak men

A

Skeletons of elderly men remain at 80-90% of their peak.

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36
Q

Normal bone or osteoporotic bone?

A

Normal

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37
Q

Normal bone or osteoporotic bone?

A

Osteoporotic - note reduced density of osteoporotic trabecular bone compared to normal trabecular bone.

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38
Q

Which hormones alter Ca2+ levels?

A

– Calcitonin (Thyroid gland)
– Parathyroid hormone (PTH) (Parathyroid gland)
– Vitamin D (cholecalciferol)
– (also Growth hormone regulates Ca2+ levels)

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39
Q

Regulation of plasma Ca2+ depends on hormonal control of exchange between ECF and…..

A

– Bone (bone calcium flux; important in short-term)
– Kidneys (renal excretion)
– Intestine (GI absorption)

40
Q

Hormones involved in calcium and phosphate homeostasis

A
  • Calcitonin,
  • Parathyroid hormone
  • Vitamin D.
41
Q

What are the organs involved in regulation of homeostasis?

A
  • Bone
  • Kidney
  • GI tract
42
Q

Example of Ca2+ involvement in the function of most cells

A
  • myocontraction,
  • nerve transmission
  • coagulation of blood
  • activation or inhibition of enzymes,
  • hormone function,
  • exocytosis,
  • cell-cell interaction,
  • cell duplication,
  • 2nd messenger function
43
Q

Para thyroid hormone structure / location

A
  • small oval glands associated with thyroid
  • embedded in thyroid capsule or thyroid
  • normally 2 on each side (some have 5-6)
44
Q

PTH function

A

Major controller of Ca2+ levels

45
Q

Hormone used for fine adjustments in parathyroid gland?

A

Calcitonin

46
Q

Secretion of PTH

A

Principle (chief) cells of parathyroid gland secrete PTH in response to low blood Ca2+

47
Q

PTH detailed function

A

Increases serum Ca2+ levels
– increases bone calcium release
– promotes kidney renal tubule reabsorption
– increases absorption from small intestine (via Vit D activation)

48
Q

Why is PTH essential for life?

A

Prevents fatal hypocalcemia

49
Q

Thyroidectomy

A

Usually removes parathyroid gland - can be fatal - but PTH producing cells cluster outside parathyroid gland along trachea

50
Q

Why does PTH use bone?

A

Uses bone as a bank to maintain Ca2+ plasma levels.

51
Q

2 major effects of PTH on bone

A

1) Induces a fast Ca2+ efflux into the plasma from the small labile pool of Ca2+ in the bone fluid.
2) Stimulates bone dissolution, promotes a slow transfer into the plasma of Ca2+ and PO4,3- from the stable pool of bone minerals in bone itself.

52
Q

Osteocytic-osteoblastic bone membraned diagram

A

Entombed osteocytes and surface osteoblasts are interconnected by long cytoplasmic processes that extend from these cells and connect to one another within the caniculli. This interconnecting cell network, the osteocytic-osteoblastic bone membrane, separates the mineralised bone
from the plasma in the central canal. Bone fluid lies between the membrane and the mineralised bone.

53
Q

Fast exchange of Ca2+ between bone and plasma.

A

Ca2+ is moved from the labile pool in the bone fluid into the plasma by PTH-activated Ca2+ pumps located in the osteocytic-osteoblastic bone membrane.

53
Q

Fast exchange of Ca2+ between bone and plasma.

A

Ca2+ is moved from the labile pool in the bone fluid into the plasma by PTH-activated Ca2+ pumps located in the osteocytic-osteoblastic bone membrane.

54
Q

Slow exchange of Ca2+ between bone and plasma.

A

Ca2+ is moved from the stable pool in the mineralised bone into the plasma through PTH-induced dissolution of the bone by osteoclasts.

55
Q

What is the osteocyti-osteoblastic bone membrane formed by?

A

Cytoplasmic extensions of interconnected osteocytes and osteoblasts.

56
Q

Calcitonin source

A

From C cells (parafollicular cells) of thyroid gland

57
Q

How many amino acids in calcitonin?

58
Q

When is calcitonin secreted?

A

High plasma Ca2+ = high calcitonin secretion

59
Q

Function of calcitonin

A
  • antagonist to PTH
  • lowers plasma Ca2+ and phosphate levels
  • inhibits bone osteoclasts and osteoblasts
  • stimulates Ca2+ secretion via kidneys
  • increases production of inactive Vit D - 24,25DHCC
60
Q

When is calcitonin important?

A

Only during hypercalcemia

61
Q

Effects of deficiencies of calcitonin?

62
Q

Feedback: PTH and calcitonin secretion diagram

63
Q

Sources of vit D

A
  • Cholesterol derivative when exposed to
    sun
  • Supplemented by diet
64
Q

What is vit D activated by?

A

Liver, then kidneys

65
Q

Function of Vit D x 3

A
  • Essential for GI calcium and phosphate absorption
  • Increases renal calcium reabsorption
  • Regulates activity of osteoblasts and osteoclasts
66
Q

Vit D when first enters the blood

A

Biologically inactive

67
Q

Requirements to activate vit D and location

A

Requires 2 sequential biochemical alterations; adding hydroxyl groups:

  1. Occurs in the liver
  2. Occurs in the kidney
68
Q

End result of adding hydroxyl groups to vit D?

A

End result is active vitamin D (calcitriol)

69
Q

What are the kidney enzymes involved in step 2 of vit D activation stimulated by>

A

PTH in response to a fall in plasma Ca2+

70
Q

Vit D skin - sunlight diagram

71
Q

Interactions between PTH and vitamin D in controlling plasma calcium diagram

72
Q

Control of plasma Phosphate diagram

73
Q

What are primary disorders in Ca2+ metabolism related to?

A

Too much or too little PTH or vitamin D deficiency.

74
Q

Disorders in Ca2+ metabolism x 5

A
  • Hypercalcemia
  • PTH Hyposecretion (hypoparathyroidism)
  • Excessive mobilisation of Ca2+ and PO4,3- from skeletal stores
  • PTH Hypersecretion (hyperparathyroidism)
  • Increased incidence of Ca2+ containing Kidney stones
75
Q

PTH Hypersecretion (hyperparathyroidism)

A

Hyper secreting tumour in one of the PTH glands – characterised by hypercalcemia and hypophosphatemia

76
Q

Possible consequences of PTH Hypersecretion (hyperparathyroidism)?

A

Reduced excitability of nerves and muscles – muscle weakness, neurological disorders, decreased alertness, poor memory and depression. Cardiac disturbances may also occur.

77
Q

What does excessive mobilisation of Ca2+ and PO4,3- from skeletal stores lead to?

A

Bone thinning

78
Q

Possible consequence excessive mobilisation of Ca2+ and PO4,3- from skeletal stores

A

Skeletal deformities and increased incidence of fractures

79
Q

Increased incidence of Ca2+ containing Kidney stones, how?

A

Excessive calcium filtering through kidneys may precipitate.

80
Q

Possible consequences of kidney stones

A

Extreme pain as stone passes through the ureters.

81
Q

Hypercalcemia ocnsequence

A
  • Peptic ulcers,
  • Nausea
  • Constipation.
82
Q

What does PTH Hyposecretion (hypoparathyroidism) lead to?

A

Hypocalcemia and hyperphosphatemia

83
Q

Symptoms of PTH Hyposecretion (hypoparathyroidism).

A

Increased neuro muscular excitability (reduced Ca2+ level)

84
Q

Possible consequences of PTH Hyposecretion (hypoparathyroidism).

A

Muscle cramps and twitches from spontaneous activity in motor nerves and tingling and pins and needles sensations result from spontaneous activity in sensory neurons.
Mental changes including irritability and paranoia.

85
Q

Total removal of PTH

86
Q

PTH Hyposecretion (hypoparathyroidism) old cause

A

Used to be due to inadvertent removal of parathyroid glands during surgical removal of the thyroid.

87
Q

Vitamin D deficiency

A

Impaired intestinal absorption of Ca2+.

88
Q

Vit D deficiency diseases

A

Rickets (children)

Osteomalacia (adults)

89
Q

Consequence of Vitamin D deficiency

A

Bone matrix not properly mineralised, Ca2+ salts not there for deposition.
Bone becomes soft and deformed, bowing under the pressure of weight bearing.

90
Q

PTH in vitamin D deficiency

A

In the face of reduced Ca2+ uptake PTH maintains plasma Ca2+ levels at the expense of bone

91
Q

Summary calcitonin from thyroid gland function

A
  1. fine adjustments
  2. lowers Ca2+
  3. antagonist to PTH
  4. inhibits bone osteoclasts and osteoblasts
  5. stimulates Ca2+ secretion via kidneys
  6. increases production of inactive Vitamin D
92
Q

PTH from Parathyroid gland

Principle (chief) ‘C cells’, function.

A
  1. major controller
  2. increases Ca2+
  3. antagonist to calcitonin
  4. increases bone Ca2+ release
  5. promotes kidney renal tubule reabsorption
  6. increases absorption from small intestine (via Vit D activation)
93
Q

wont be asked on

A

ovaries and testes!

94
Q 
Vitamin D
(cholecalciferol) synthesized from cholesterol when exposed to sun dietary intake
activated by liver then kidneys, function
A
  1. increases GI and renal Ca2+ absorption
  2. regulates activity of osteoblasts and
    osteoclasts

Physiology (28 decks)

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